The present invention relates generally to a computer model of diabetes. More specifically, the present invention relates to a computer model of diabetes (e.g., human type 2 diabetes) within the framework of multiple macronutrient metabolism.
The process of extracting energy from the environment and using it to maintain life is called metabolism. Every cell in the human body requires a constant supply of energy in order to avoid the decay to thermodynamic equilibrium (i.e. death). The required energy comes from the ingestion of food and the carefully controlled oxidation of the carbon based macronutrients: carbohydrates, fats, and protein. The fact that humans don't eat continuously, and can survive for some period of time without food, implies that we have the ability to store nutrients for use between meals. Evolution has provided us with complex control mechanisms involving multiple organ systems that direct the storage, mobilization, and utilization of various fuels under a variety of environmental conditions including feeding of various diets, fasting, and performing physical activity.
Diabetes is a complex disease resulting from alterations in normal metabolism that are manifest in elevated fasting and post-prandial blood glucose, impaired insulin sensitivity in muscle, liver and adipose tissue, as well as impaired pancreatic function. The development of pharmaceutical treatments for this disease typically focuses on affecting these general pathways. Complex interactions between these and other pathways, however, make the selection of the appropriate intervention sites and the efficacy of drug candidates difficult to predict. Furthermore, although diabetes is typically characterized by abnormal glucose regulation, impaired fat and protein metabolism play an important role (McGarry, Science, 258: 766-70, 1992).
Because of the complexity of metabolic control mechanisms, mathematical and computer models of the processes directing metabolism can be used to help better understand human metabolism and make useful predictions. For example, several researchers have constructed simple mathematical models of glucose regulation and its hormonal control (Cobelli et al., Math. Biosci., 58:27-60, 1982, Guyton et al., Diabetes, 27:1027-42, 1978. Srinivasan et al., Comp. Biomed. Res., 3:146-66, 1970, Cramp et al., Biological Systems, Modeling and Control, D A Linkens ed. pp 171-201, 1979) Some researchers have attempted to represent diabetes related disorders, but these models were restricted to glucose regulation and did not represent the important interactions with fat or protein metabolism (Cobelli et al., Math. Biosci., 58:27-60, 1982). Fat metabolism in particular is thought to play a major role in diabetes related disorders (McGarry, Science, 258: 766-70, 1992).
Hence, there is a need to develop a computer model of diabetes within the framework of multiple macronutrient metabolism.